Division of Gastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital Taipei Branch, Taipei, Taiwan; Graduate Institute of Clinical Medicine, Buddhist Tzu Chi General Hospital Taipei Branch, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
BACKGROUND & AIMS:
Chronic hepatitis B patients with high viral loads are at increased risk of cirrhosis and hepatocellular carcinoma (HCC). In those with low viral loads, higher hepatitis B surface antigen (HBsAg) levels have been shown to predict HCC development. However, little is known about the difference in risk for other hepatitis B virus (HBV)-related adverse outcomes with varying HBsAg levels.
A total of 1068 Taiwanese hepatitis B e antigen (HBeAg)-negative HBV carriers with serum HBV DNA level <2000 IU/mL at baseline were followed for a mean duration of 13.0 years. Patients were categorized based on their HBsAg levels, and the relationships between HBsAg level and development of HBeAg-negative hepatitis, hepatitis flare, and cirrhosis were investigated.
Of the 1068 patients with low viral loads, 280 developed HBeAg-negative hepatitis with an annual incidence rate of 2.0%. HBsAg level, but not HBV DNA level, was found to be a risk factor for HBeAg-negative hepatitis. Multivariate analysis showed that the adjusted hazard ratio in patients with HBsAg level ≧1000 versus <1000 IU/mL was 1.5 (95% confidence interval, 1.2-1.9). The positive correlation was present when evaluating other endpoints, including hepatitis flare and cirrhosis, and remained consistent when the study population was restricted to those with normal alanine aminotransferase (ALT) level at baseline. The annual incidence rate of HBeAg-negative hepatitis was lowered to 1.1% in those with low levels of HBV DNA, HBsAg, and ALT.
In HBeAg-negative patients with low viral loads and genotype B or C virus infection, a higher HBsAg level can predict disease progression. HBsAg <1000 IU/mL in combination with low levels of HBV DNA and ALT help define minimal-risk HBV carriers.